Smaller Brain Regions Presage Drift into Alzheimer's

Action Points

Explain to interested patients that this preliminary study suggests that in patients with mild cognitive impairment, the volume of the hippocampus, the region of the brain central to learning and memory, may be predictive of the likelihood that the patient will go on to develop Alzheimer's disease, stay stable, or improve.

LOS ANGELES, May 9 â€” Patients with mild cognitive impairment who have smaller-than-average hippocampal volumes are more likely to progress from mild cognitive impairment to Alzheimer's disease, researchers here have found.

Those with mild cognitive impairment who develop Alzheimer's also have evidence of greater atrophy of specific regions of the hippocampus, reported Liana G. Apostolova, M.D., and colleagues, of the University of California at Los Angeles.

In contrast, patients with larger hippocampal volumes are more likely to either remain mildly impaired or improve over time, the authors wrote in the May 8 issue of Archives of Neurology.

In a study of 20 patients with mild cognitive impairment who were followed for three years with clinical and neuropsychologic evaluations, the authors found that patients who had greater atrophy of the CA1 region and subiculum of the hippocampus were significantly more likely to convert to Alzheimer's than those in whom the structures were unchanged or only slightly changed.

"Some studies find that a proportion of mild cognitive impairment subjects revert back to normal cognition when followed up longitudinally," they wrote. "To our knowledge, ours is the first imaging study that includes the whole spectrum of clinical outcomes of cognitive worsening, improvement, and stability."

Although studies have shown that most patients diagnosed with mild cognitive impairment will go on the develop Alzheimer's disease, there are some whose cognitive impairment remains stable, and still others who improve.

To see whether hippocampal volume could be predictive of conversion to Alzheimer's disease, stability, or improvement in these patients, the authors conducted a prospective longitudinal cohort study of 20 patients with mild cognitive impairment.

They performed baseline regional hippocampal studies using 3-D hippocampal mapping techniques to determined the degree of atrophy in the regions of interest, and then followed the patients to see how the baseline values would correlate with change in cognitive function.

During the study, six patients went on to develop frank Alzheimer's disease, seven remained stable, and seven had cognitive improvement.

The authors determined that those patients who developed Alzheimer's had 9% smaller left mean hippocampal volumes, and 13% smaller right mean volumes compared with patients in whom there was no change in cognitive status. Compared with patients who showed cognitive improvement, the patients who developed Alzheimer's had 24% smaller left hippocampal volumes, and 27% smaller right volumes (all differences were statistically significant on the t test).

When they performed a volumetric analysis, they also detected a trend toward greater hippocampal atrophy in those with no change in cognitive status relative to those who improved over the course of the study. However, this difference (16%) was not statistically significant.

They also detected differences in the subiculum between those who progressed to Alzheimer's those with no change, and between the no-change group and those who improved.

"Multiple linear regression analysis confirmed the group effect to be highly significant and independent of age, hemisphere, and Mini-Mental State Examination scores at baseline," the authors noted.

Because they had excluded from their study patients with depression or other illnesses that might contribute to cognitive decline, they were unable to explain the origin of the amnestic syndrome in those patients with mild cognitive impairment who improved over the course of the study.

Our findings cannot be generalized to all mild cognitive impairment patients, especially to those with the nonamnestic subtype," the investigators acknowledged. "A large prospective study that follows up patients with all mild cognitive impairment subtypes over time is needed to address the etiological, clinical, and prognostic questions that remain unanswered."

Reviewed by Robert Jasmer, MD Assistant Professor of Medicine, University of California, San Francisco

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